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Journal of Virology, January 2005, p. 661-667, Vol. 79, No. 1
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.1.661-667.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Natural Killer Cells Utilize both Perforin and Gamma Interferon To Regulate Murine Cytomegalovirus Infection in the Spleen and Liver

Joy Loh,1 Dortha T. Chu,2 Andrew K. O'Guin,1 Wayne M. Yokoyama,2 and Herbert W. Virgin IV1*

Departments of Pathology and Immunology and Molecular Microbiology,1 Howard Hughes Medical Institute, Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri2

Received 9 March 2004/ Accepted 26 August 2004

Natural killer (NK) cells are critical for innate regulation of the acute phase of murine cytomegalovirus (MCMV) infection and have been reported to utilize perforin (Pfp)- and gamma interferon (IFN-{gamma})-dependent effector mechanisms in an organ-specific manner to regulate MCMV infection in the spleen and liver. In this study, we further examined the roles of NK cells, Pfp, and IFN-{gamma} in innate immunity to MCMV infection. With the recently described NK cell-deficient (NKD) mouse, we confirmed previous findings that NK cells, but not NKT cells, are required for control of the acute phase of MCMV infection in spleen and liver cells. Interestingly, we found that Pfp and IFN-{gamma} are each important for regulating MCMV replication in both the spleen and the liver. Moreover, NK cells can regulate MCMV infection in the spleens and livers of Pfp–/– mice in a Pfp-independent manner and can use an IFN-{gamma}-independent mechanism to control MCMV infection in IFN-{gamma}–/– mice. Thus, contrary to previous reports, NK cells utilize both Pfp and IFN-{gamma} to control MCMV infection in the spleen and liver.

* Corresponding author. Mailing address: Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Ave., Box 8118, St. Louis, MO 63110. Phone: (314) 362-9223. Fax: (314) 362-4096. E-mail: virgin{at}immunology.wustl.edu.

Journal of Virology, January 2005, p. 661-667, Vol. 79, No. 1
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.1.661-667.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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